title: Structural basis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch.
abstract: The tetracycline aptamer is an in vitro selected RNA that binds to the antibiotic with the highest known affinity of an artificial RNA for a small molecule (Kd approximately 0.8 nM). It is one of few aptamers known to be capable of modulating gene expression in vivo. The 2.2 A resolution cocrystal structure of the aptamer reveals a pseudoknot-like fold formed by tertiary interactions between an 11 nucleotide loop and the minor groove of an irregular helix. Tetracycline binds within this interface as a magnesium ion chelate. The structure, together with previous biochemical and biophysical data, indicates that the aptamer undergoes localized folding concomitant with tetracycline binding. The three-helix junction, h-shaped architecture of this artificial RNA is more complex than those of most aptamers and is reminiscent of the structures of some natural riboswitches.
authors.affiliation: Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Edwards
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Ferré-D'Amaré
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013379:Substrate Specificity; D013752:Tetracycline / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D052157:Aptamers, Nucleotide; D014867:Water; D013752:Tetracycline